Interferon regulatory factor-4 activates IL-2 and IL-4 promoters in cooperation with c-Rel.

Interferon regulatory factor (IRF)-4 is a member of the IRF transcription factor family, whose expression is primarily restricted to lymphoid and myeloid cells. In T-cells, IRF-4 expression is induced by T-cell receptor (TCR) cross-linking or treatment with phorbol-12-myristate-13-acetate (PMA)/Ionomycin, and IRF-4 is thought to be a critical factor for various functions of T-cells. To elucidate the IRF-4 functions in human adult T-cell leukemia virus type 1 (HTLV-1)-infected T-cells, which constitutively express IRF-4, we isolated IRF-4-binding proteins from T-cells, using a tandem affinity purification (TAP)-mass spectrometry strategy. Fourteen proteins were identified in the IRF-4-binding complex, including endogenous IRF-4 and the nuclear factor-kappaB (NF-κB) family member, c-Rel. The specific association of IRF-4 with c-Rel was confirmed by immunoprecipitation experiments, and IRF-4 was shown to enhance the c-Rel-dependent binding and activation of the interleukin-4 (IL-4) promoter region. We also demonstrated that IL-2 production was also enhanced by exogenously-expressed IRF-4 and c-Rel in the presence of P/I, in T-cells, and that the optimal IL-2 and IL-4 productions in vivo was IRF-4-dependent using IRF-4-/- mice. These data provide molecular evidence to support the clinical observation that elevated expression of c-Rel and IRF-4 is associated with the prognosis in adult T-cell leukemia/lymphoma (ATLL) patients, and present possible targets for future gene therapy

Empirical Research on Vulnerability and Value of〈Care Labor〉(2) “working consciousness” of people with disabilities support/care professionals ; supported by the granted research from Mizuho Welfare Foundation.

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Relation of Heart-Rate Recovery to New Onset Heart Failure and Atrial Fibrillation in Patients With Diabetes Mellitus and Preserved Ejection Fraction

Diabetic autonomic neuropathy is a possible link between abnormal metabolism in type 2 diabetes mellitus (T2DM) and risk for atrial fibrillation (AF) and heart failure (HF). The aim of this study was to elucidate the association between attenuated heart rate recovery (HRR) and these manifestations of myocardial dysfunction in T2DM. Nine hundred fourteen consecutive patients with T2DM (mean age 56 +/- 11 years, 508 men) without diabetes mellitus complications, with negative results on stress echocardiography, were enrolled. Patients with known cardiac disease were excluded. Demographics, clinical assessment, co-morbidities, and insulin use were collected prospectively. The association of HRR with new-onset HF and AF was sought using a Cox proportional-hazards model. There were 47 events (22 HF and 25 AF) during a median follow-up period of 7.8 years. Events were associated with age, exercise capacity, HRR, and left atrial volume index but not with baseline glycosylated hemoglobin, left ventricular mass index, or standard markers of diastolic function. In sequential Cox models for the combined outcomes, the model based on clinical data (age and gender; overall chi-square = 5.5) was not significantly improved by left atrial volume index (chi-square = 8.6, p = 0.10) or maximum METs (chi-square = 8.7, p = 0.07) but was significantly improved by adding HRR (chi-square = 19.7, p = 0.004). In addition, HRR provided significant incremental prognostic value regarding the composite end point (net reclassification improvement 19.2%, p = 0.04; integrated discrimination improvement 1.58%, p = 0.004). In conclusion, the association of HRR with subsequent HF and AF, independent of and incremental to left atrial volume index and other markers of abnormal cardiac structure and function, indicates a role for autonomic neuropathy as the link between metabolic and cardiac risk in patients with T2DM. (c) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:748-753

Incremental value of three-dimensional echocardiography in the evaluation of left ventricular size in mitral regurgitation: a follow-up study after mitral valve surgery

Background Increased left ventricular (LV) dimensions are an indication for surgery in patients with asymptomatic mitral regurgitation, but M-mode or two-dimensional measurements have known limitations. The aim of this study was to determine the value of three-dimensional echocardiography in predicting postoperative outcomes after mitral surgery. Methods Sixty-seven patients with severe asymptomatic or minimally symptomatic mitral regurgitation (69% men; mean age, 62 ± 13 years) who underwent mitral valve surgery from January 2010 to December 2011 were studied. In addition to standard echocardiography, baseline three-dimensional echocardiography was performed for accurate quantification of LV size. Patients were followed over a median time of 1 month (interquartile range, 0-8 months) for postoperative development of atrial fibrillation or LV dysfunction. A multivariate regression analysis was performed to identify associations with events. Results Postoperative LV dysfunction developed in 15 patients (22%), and 21 patients (31%) had postoperative atrial fibrillation. There was no association between two-dimensional end-systolic volume index and outcomes (hazard ratio, 1.02; P =.18). Postoperative atrial fibrillation or LV dysfunction was associated with baseline three-dimensional LV end-systolic volume index (hazard ratio, 1.06; 95% confidence interval, 1.04-1.16), independent of age and presence of coronary artery disease. LVESVi ≥ 40 mL/m was the best cutoff value to predict postoperative events (sensitivity, 80%; specificity, 85%). After adding LVESVi to a model containing clinical and echocardiographic parameters, net reclassification improvement was 0.27 (95% confidence interval, 0.25-0.29; P =.024). Conclusions LVESVi from three-dimensional echocardiography is an independent predictor of postoperative outcomes in patients with severe mitral regurgitation that is incremental to other clinical and echocardiographic variables